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Biomedical subjects

R Lo

Publications and source records attributed to R Lo.

At least 37 records · Page 2Linked to original sources

Transducin-like Enhancer of split 2, a mammalian homologue of Drosophila Groucho, acts as a transcriptional repressor, interacts with Hairy/Enhancer of split proteins, and is expressed during neuronal development.

Groucho is a Drosophila transcriptional repressor involved in neurogenesis, segmentation, and sex determination together with basic helix-loop-helix proteins of the Hairy/Enhancer of split (HES) family. Several mammalian Groucho homologues, the Transducin-like Enhancer of split (TLE) 1 through 4 proteins, share similar properties with their Drosophila counterpart, suggesting that TLE proteins perform functions analogous to the roles of Groucho in Drosophila. The aim of this study was to examine this possibility by characterizing the properties of TLE2 and extending the analysis of TLE1. It is shown here that TLE2 and TLE1 are transcriptional repressors that contain two separate repression domains, located either within a Gln-rich amino terminal region or within an internal domain characterized by an abundance of Ser, Thr, and Pro residues. In addition, both TLE2 and TLE1 can homo- and heterodimerize through a short region that is part of their amino-terminal transcription repression domains. Finally, TLE2 interacts and is co-expressed with mammalian HES proteins in both neural and non-neural tissues. Taken together, these findings implicate TLE2 in transcriptional repression and define the structural elements that mediate transcriptional and protein-protein interaction functions of Groucho/TLE proteins.

Animals↗

Arabidopsis LEAFY COTYLEDON1 is sufficient to induce embryo development in vegetative cells.

The Arabidopsis LEAFY COTYLEDON1 (LEC1) gene is required for the specification of cotyledon identity and the completion of embryo maturation. We isolated the LEC1 gene and showed that it functions at an early developmental stage to maintain embryonic cell fate. The LEC1 gene encodes a transcription factor homolog, the CCAAT box-binding factor HAP3 subunit. LEC1 RNA accumulates only during seed development in embryo cell types and in endosperm tissue. Ectopic postembryonic expression of the LEC1 gene in vegetative cells induces the expression of embryo-specific genes and initiates formation of embryo-like structures. Our results suggest that LEC1 is an important regulator of embryo development that activates the transcription of genes required for both embryo morphogenesis and cellular differentiation.

Amino Acid Sequence↗

Combinatorial expression patterns of individual TLE proteins during cell determination and differentiation suggest non-redundant functions for mammalian homologs of Drosophila Groucho.

The Drosophila protein Groucho is involved in the regulation of cell-determination events during insect neurogenesis and segmentation. A group of mammalian proteins, referred to as transducin-like Enhancer of split (TLE) 1 through 4, share with Groucho identical structures and molecular properties. The aim was to determine whether individual TLE proteins participate in the regulation of cell determination in mammals like their Drosophila counterpart. It is here reported that TLE family members are expressed in combinatorial ways during the in vitro differentiation of mouse P19 embryonic carcinoma cells (a model for neural determination) and rat CFK2 cells (a model for chondrocytic determination). TLE1 is up-regulated and TLE2 and TLE4 are down-regulated to different extents during early stages of differentiation. In contrast, later stages correlate with up-regulation of TLE2 and TLE4, and decreased expression of TLE1. Individual TLE proteins are also expressed in combinatorial as well as complementary patterns during the development of the cerebral cortex and spinal cord of mouse embryos. In particular, TLE1 is robustly expressed in both neural progenitor cells and postmitotic neurons of the outer layers of the cortical plate, whereas TLE4 expression marks preferentially postmitotic neurons of the inner layers. Taken together, these results strongly suggest non-redundant roles for individual TLE proteins during both cell-determination and cell-differentiation events.

Animals↗

Pain in Chinese cancer patients under palliative care.

Over a 4-month period, 218 Chinese patients with advanced cancer were admitted to a palliative care unit in Hong Kong. Ninety-five (44%) of them had pain. Of these 95, 70 (mean age 61.7 years) were evaluated with the visual analogue scale (VAS) and the numerical rating scale (NRS). Forty-two per cent of the 70 patients were illiterate. Eighty-three per cent had metastases. Eighty-seven per cent had pain due to the disease process. Forty-nine per cent had more than one pain, 54% had moderate pain and 20% had severe pain. The most common primary tumour was lung cancer. NRS scores strongly correlated with corresponding VAS scores, suggesting that NRS can routinely be used for pain intensity assessment in the Chinese. The study also showed that 64% of these patients with pain had moderate to severe disabilities to the basic activity of daily living, although there was no correlation between the severity of pain and the severity of disability.

Adult↗

A holistic approach in facilitating adherence in people with diabetes.

The issue of adherence is a multidimensional one, with a complex set of factors that affect the behaviour of people with chronic illness. This article draws on some of the results of a recent study which explored the psychosocial factors affecting adherence to self-care behaviours in people with diabetes mellitus (DM).

Adaptation, Psychological↗

Affinity for the nuclear compartment and expression during cell differentiation implicate phosphorylated Groucho/TLE1 forms of higher molecular mass in nuclear functions.

The Drosophila protein Groucho is involved in embryonic segmentation and neural development, and is implicated in the Notch signal transduction pathway. We are investigating the molecular mechanisms underlying the function of Groucho and of its mammalian homologues, the TLE ('transducin-like Enhancer of split') proteins. We show that Groucho/TLE1 proteins are phosphorylated. We also show that two populations of phosphorylated Groucho proteins can be identified based on their interaction with the nuclear compartment. More slowly migrating proteins with an apparent molecular mass of roughly 110 kDa interact strongly with the nuclei, while faster migrating proteins displaying molecular masses roughly 84-85 kDa show lower affinity for the nuclear compartment. Similarly, TLE1 proteins with an apparent molecular mass of roughly 118 kDa exhibit higher affinity for the nuclear compartment than do faster migrating forms with apparent molecular masses of 90-93 kDa. Moreover, we show that the nuclear, more slowly migrating, TLE1 proteins are induced during neural determination of P19 embryonic carcinoma cells. These results implicate phosphorylation in the activity of Groucho/TLE1 proteins and suggest that phosphorylated forms of higher molecular mass are involved in nuclear functions. Finally, we show that different TLE proteins respond in different ways to the neural commitment of P19 cells, suggesting that individual members of this protein family may have non-redundant functions.

Animals↗

A survey of people with diabetes in northern New South Wales: problems with self-care.

People with diabetes mellitus (DM) completed a questionnaire (n = 255) which surveyed the management of their disease and its complications. The questionnaire sought information on: (i) frequency of testing blood and urine; (ii) management of diet and weight control; and (iii) the incidence of smoking and alcohol consumption among people with diabetes. The aims of the study included the identification of the prevalence of coronary heart disease (CHD) among people with diabetes in the northern rivers region of New South Wales; to investigate the problems encountered by people with diabetes in the management of their disease and whether or not there were differences as a function of age and gender. Results indicated that females visited their dietitians more recently and consumed less alcohol than males. Males exercised a great deal more, both in frequency and duration than females. Older respondents tested their blood and urine less frequently, and had less difficulty adhering with diet requirements than younger respondents. Younger respondents expressed greater difficulty in living appropriately with their condition and reducing alcohol consumption. Differences between patients with DM and those with added heart complications indicated that the amount of alcohol consumed was higher and exercise was more likely to be prescribed by medical practitioners for those with CHD. They also found it more difficult to exercise regularly. The role of the health professionals in facilitating self-care is discussed in the light of these findings.

Adolescent↗

The development and evaluation of a computer-aided diabetes education program.

This paper describes the development and evaluation of a computer-aided learning (CAL) program. The program was tested in a trial that involved 36 people with diabetes; 20 received CAL lessons in diabetes management and 16 attended conventional diabetes classes conducted by diabetes educators. When measurements taken before and three months after the education were compared, both groups showed significant improvement in their knowledge; the blood glucose levels of the CAL group were significantly lower but those of the conventional education group were higher. This means that the CAL program was as effective as conventional education in imparting knowledge but it was more likely to motivate people to control their glucose levels. The CAL program allows diabetes educators to spend less time on education in basic knowledge and to concentrate more on motivational and social factors that are important determinants of patient compliance. It can also benefit people with diabetes whose access to health professionals and/or conventional diabetes education is restricted.

Adult↗

The role of transrectal ultrasound-guided biopsy-based staging, preoperative serum prostate-specific antigen, and biopsy Gleason score in prediction of final pathologic diagnosis in prostate cancer.

OBJECTIVES: To evaluate the role of ultra sound-guided systematic and lesion-directed biopsies, biopsy gleason score, preoperative serum prostate-specific antigen (PSA) as three objective and reproducible variables to provide a reliable combination in preoperative identification of risk of extraprostatic extension in patients with clinically localized prostate cancer. METHODS: The case records of 813 patients who underwent radical prostatectomy for clinically localized prostate cancer were analyzed. All had multiple systematic biopsies, two to three from each lobe, in addition to lesion-directed biopsies. Additionally, biopsies were done on seminal vesicles (SVs), if abnormal. Based on biopsy results, patients were classified as having stage B1 (T2a-T2b) or B2 (T2c) disease, depending on whether biopsies from one or both lobes were positive and stage C (T3) if there was evidence of SV involvement by biopsy of biopsies from areas of extracapsular extension as seen on transrectal ultrasound (TRUS) were positive. Logistic regression analyses with log likelihood chi-square test was used to define the correlation between individual as well as combination of preoperative variables and pathologic stage. RESULTS: On final pathologic examination, 473 (58%) patients had organ-confined disease, 188 (23%) had extracapsular extension (ECE), with or without positive surgical margins, and 72 (9%) had SV involvement. Eighty (10%) patients had pelvic lymph node metastases. Biopsy-based staging was superior to clinical staging in predicting final pathologic diagnosis. Logistic regression analyses revealed that the combination of biopsy-based stage, preoperative serum PSA, and biopsy Gleason score provided the best prediction of final pathologic stage. Probability plots constructed with these data can provide significant information on risk of extraprostatic extension in individual patients. CONCLUSIONS: This study demonstrates that TRUS-guided systematic biopsy in combination with preoperative serum PSA and biopsy Gleason score may provide a cost-effective approach for management decisions and prognostication in patients with prostate cancer.

Biopsy↗

Cytogenetic abnormalities in two cases of neuroblastoma.

Neuroblastomas are common solid tumors in children. We report chromosome analysis of two neuroblastomas, each studied at diagnosis and at recurrence. The first case was a clinical stage D tumor which showed 45,X-Y, add(1)(p34),der(15)t(Y;15)(q11;p13), and double minutes on cytogenetic analysis at diagnosis. At recurrence, the same structural abnormalities were present along with a homogeneously staining region (hsr) at 8q22, 19p12, or 3p23 in each of three related clones. The hsr were shown to represent amplification of the N-myc gene by in situ hybridization. Cytogenetic analysis of the second tumor, stage D-S, showed 48-54,XX,der(1)add (1)(q41), +2, +7, +7, inv(9), +17, + mar. The lack of demonstrative involvement of 1p or visible evidence of gene amplification has also characterized the limited number of D-S specimens previously described, suggesting that stage D-S neuroblastoma indeed differs from stage D disease at the genetic level.

Abdominal Neoplasms↗

Chromosome analysis of nine endocrine neoplasms of the pancreas.

Endocrine neoplasms of the pancreas differ from the more common adenocarcinomas of the pancreas not only in histologic appearance, but also in clinical presentation and biologic behavior. Chromosomes were analyzed from nine fresh pancreatic endocrine neoplasms. Clonal chromosomal abnormalities were found in five; all were malignant neoplasms. One showed only a loss of the Y chromosome and another had a small triploid population of cells in addition to a normal mainline, with a karyotype of 61-66,XX, -X, -1, -2, -3, -4, +5, -6, +7, -11, -14, +17, +18, +20, +mar1,x2, +mar2,inc. Three neoplasms had near-haploid clones. One neoplasm had a composite karyotype of 31-36 ,X, +1, +3, +5, +7, +9, +10, +17, +18, +mar. Two were from the same patient, who had the autosomal dominant syndrome MEN-1. The same clone, described as 29 ,X, +add(1)(p12), +5, +7, +8, +18, +19, was found in both the primary pancreatic neoplasm and in the metastatic tumor. To our knowledge, this is the first report of a haploid clone in both a primary and metastatic solid tumor, and suggests that the near-haploid state is at least compatible with metastasis. These data, combined with the limited reports of cytogenetic data from endocrine pancreatic neoplasms, suggest that at least half of such neoplasms will have an abnormal karyotype.

Adult↗

Utility of preoperative serum prostate-specific antigen concentration and biopsy Gleason score in predicting risk of pelvic lymph node metastases in prostate cancer.

OBJECTIVES: To determine the accuracy of the preoperative serum concentration of prostate-specific antigen (PSA) plus the Gleason pathology score of biopsy specimens in predicting the presence of disease in the pelvic lymph nodes in patients with prostate cancer. METHODS: The medical records of all patients treated for prostate cancer at eight medical centers from January 1988 to June 1993 were reviewed. There were 932 patients with newly diagnosed prostate cancer for whom all relevant data were available who had undergone pelvic lymphadenectomy with (n = 912) or without (n = 20) radical prostatectomy. The rate of false-negative predictions of metastases based on combined preoperative biopsy Gleason score and serum PSA concentration was analyzed. A multivariate logistic regression analysis was performed to assess the value of preoperative serum PSA and biopsy Gleason scores individually and in combination in predicting pelvic lymph node metastases. RESULTS: The false-negative rate of metastases was 0% for preoperative PSA concentrations < or = 6 ng/mL and biopsy Gleason scores < or = 5 (n = 142) and 1.0% for PSA concentrations < or = 10 ng/mL and Gleason scores < or = 6 (n = 388). The 95% upper confidence limit for the rate of false negativity at this PSA cut-off level was 2.0%. A combination of preoperative serum PSA levels and biopsy Gleason scores provided the best prediction for the false-negative rates. CONCLUSIONS: For patients with newly diagnosed prostate cancer who have biopsy Gleason scores < or = 6 and preoperative PSA concentrations < or = 10 ng/mL (42% of our series), a staging pelvic lymphadenectomy appears to be unnecessary. The substantial cost associated with both cross-sectional imaging and staging lymphadenectomy may therefore be avoidable in this group of patients.

Biopsy↗

A new 3C syndrome: cerebellar hypoplasia, cavernous haemangioma and coarctation of the aorta.

Two children were identified with facial haemangioma, cerebellar hypoplasia and co-arctation of the aorta; the second child presented to the neurology department because of facial haemangioma. The importance of awareness of the association of these three conditions is essential to ensure proper management and survival of this group of patients. The possible pathophysiology of these associated conditions is discussed.

Aortic Coarctation↗

Electric injury with cerebral venous thrombosis. Case report and review of the literature.

BACKGROUND AND PURPOSE: A case of accidental electrocution with previously unreported arteriographic evidence of cerebral vein thrombosis is presented. A brief description of early and late neurological complications and current theories attempting to explain the histopathological findings of electric injury are reviewed. The occurrence and persistence of late neurological complications are elucidated. CASE DESCRIPTION: A report of an accidental electrocution with 800 V of alternating current in a young man is presented. Cerebral angiography showed a cerebral vein thrombosis. The immediate complications included loss of consciousness, confusion, memory loss, and headache. Late complications of right-sided clumsiness, sensory loss, hemianopsia, and neglect persisted for more than 1 year despite the brain being outside the current pathway. CONCLUSIONS: High-voltage electric injury may cause cerebral vein thrombosis with significant early and delayed brain injury even when the brain lies outside the current pathway.

Adult↗

Transient global amnesia after cerebral angiography with iohexol.

Transient global amnesia is an unusual neurologic phenomenon that occasionally occurs after angiography, usually of the cerebral vessels. It represents a benign event, and normal function is ultimately restored, but the amnesia may be frightening for both the patient and the physician until its nature is recognized. The authors describe two cases of transient global amnesia occurring after cerebral angiography with iohexol, outline the criteria for the diagnosis and discuss the proposed mechanism of the phenomenon.

Adult↗

Rapid alteration of synaptic number and postsynaptic thickening length by NMDA: an electron microscopic study in the occipital cortex of postnatal rats.

The N-methyl-D-aspartate (NMDA) receptor has been widely implicated in numerous activity-dependent models of neural plasticity, learning, and memory. The formation of new synapses is a major assumption of the neural basis of learning. The current research was conducted to determine whether NMDA receptor activation could induce synaptic formation and, if so, whether this ability would mirror developmental changes in NMDA receptors. Rats at various developmental ages were given a single intraperitoneal injection of NMDA and sacrificed at various brief postinjection intervals (0.5-2 hr). The rats showed an age-dependent decline in the behavioral response to NMDA, as evidenced by reduced seizure activity and duration. Quantitative electron microscopic observations on the molecular layer of the occipital cortex, an area rich in NMDA receptors, revealed a transient increase in the length of postsynaptic thickenings in 17- and 35-day-old animals, appearing within 0.5 hr of injection. At 1 and 2 hr postinjection, an increase in synaptic density (number of synapses) was observed in 8-day-old animals. These results provide evidence that NMDA administration alone is capable of rapidly inducing alterations in synaptic structure and the formation of new synapses, underscoring the importance of the NMDA receptor in synaptogenesis and synaptic structural plasticity.

Aging↗

Arterial desaturation during induction in healthy adults: should preoxygenation be a routine?

We studied the haemoglobin saturation of one hundred healthy patients equally divided into two groups. Group 1 patients received three minutes of preoxygenation prior to thiopentone induction followed by inhalational anaesthetics. Group 2 patients breathed room air prior to induction. None of the patients in Group 1 showed any arterial oxygen desaturation during the five minutes of the induction period, whereas 21 patients in Group 2 showed definite desaturation (P less than 0.005), of which fifteen patients had a saturation of 90% or less (P less than 0.005) and six had a saturation of 85% or less. Since those were healthy patients and the anaesthetics were given by experienced anaesthetists, we concluded that some form of preoxygenation should be used in all patients receiving general anaesthesia.

Adolescent↗

AuthorBase: a database of authoring systems software.

A working prototype database of authoring system software was developed as part of a study of authoring software conducted by the National Library of Medicine. The database and development issues ranging from the scope of the database to what information to document are described. The protype demonstrates that records of reasonable integrity can be derived from vendor supplied information as long as users understand the database is only an initial starting point in searching for authoring software and a resource for becoming generally familiar with the technology.

Authorship↗